Gestational diabetes (GDM), defined as glucose intolerance first developing during gestation and disappearing after parturition, has been diagnosed in 1 to 3% of all human pregnancies. If not properly diagnosed or treated, the unborn child bears a higher risk for congenital abnormalities, perinatal morbidity and mortality. Women who are older, obese or with a family history of diabetes have a higher risk of becoming diabetic during pregnancy. More than half of the women with GDM eventually develop overt diabetes. Therefore, GDM has significant health impact on both the offspring and the mother. There is no suitable animal model of human GDM at the present time. An animal model would further our outstanding and managing of GDM and is an urgent need. Pregnancy is a period of fat deposition and lactation a period of fat mobilization. A reverse relationship has been suggested between the amount of lactation and adipose tissue mass in humans. In animal studies, the Prinicipal Investigator has observed that if repeated pregnancy were not followed by lactation, hyperglycemia and a cumulative increase in adipose tissue mass were found. Since obesity and large adipose tissue mass are associated with glucose intolerance, these multiparous rats without lactation experience may have higher risk of developing glucose intolerance during subsequent pregnancy.
The first aim of this proposed research is to verify, using a strain of obesity prone rats (Osborne-Mendel), the previous findings obtained by the PI in Sprague-Dawley rats that repeated pregnancy without lactation will produce fatter rats with glucose intolerance during the third pregnancy.
The second aim i s to test the hypothesis that enlarged adipose tissue mass is the major etiology of GDM.
Other aims of this research are to examine the long-term effects of gestational glucose intolerance on body weight regulation and glucose tolerance in adult offspring, to compare the effectiveness of different regimens (exercise or high fiber diet) in preventing or a ameliorating glucose intolerance and long-term effects of these treatments in the offspring. It is expected that data obtained from this research will demonstrate that repeated pregnancy without lactation in rats can produce glucose intolerance and insulin insensitivity in subsequent pregnancy, therefore serves an ideal animal model for human GDM.
